Roose 1998.
| Study characteristics | ||
| Methods | RCT design: 2‐arm parallel‐group trial Total N randomised: 81 Length of follow‐up: no follow‐up Analysis: ITT (4 paroxetine participants discontinued, 10 nortriptyline participants discontinued) |
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| Participants | Location: USA Number of study centres and setting: outpatients from 4 hospitals CAD criteria: MI, CABG, coronary angioplasty, positive stress test, or angiographic evidence of a 75% or greater luminal narrowing of a major coronary artery; time to randomisation unclear Depression criteria: meeting DSM‐IV criteria for major depressive disorder, unipolar subtype, with a score of 16 or greater on the 17‐item HAM‐D Other entry criteria: age >= 18 Exclusion criteria: MI within the past 3 months, a baseline QTc interval of 460 milliseconds or greater, unstable or crescendo angina, receiving drugs with class 1 antiarrhythmic activity or warfarin Treatment 1 N: 41 (12% female, mean age: 57.8 (SD: 11.0)) Treatment 2 N: 40 (22% female, mean age: 57.9 (SD: 12.7)) Comparability of groups: no significant baseline differences |
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| Interventions | Treatment 1: paroxetine (+ dummy placebo at night) (age < 65: 20 mg/d for the first 3 weeks; age > 65: 10 mg/d for the first week, 20 mg/d for week 2 and 3; if no response (HAM‐D reduction 50% or HAM‐D <= 8), 30 mg/d at week 4 and 40 mg/d at end of week 5) Treatment 2: nortriptyline (+ dummy placebo in the morning) (25 mg for the first 2 days; 50 mg on day 3; on day 7 plasma level measurement and adjustment of the dose to achieve a nortriptyline plasma level between 203 and 456 nmol/L (80 to 120 ng/mL)) Duration of treatment: 6 weeks |
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| Outcomes | Review outcomes: depression symptoms (HAM‐D), depression remission (HAM‐D ≤ 8), depression response (50% reduction on HAM‐D), cardiac events, cardiovascular vital signs (BP, HR), ECG waves, pharmacological side effects Other outcomes: heart rate variability (SDNN, pNN50), ventricular premature depolarisations |
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| Funding | Smith‐Kline Beecham Pharmaceuticals (GlaxoSmithKline) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "randomized by permuted blocks of 10" (p. 288) |
| Allocation concealment (selection bias) | Unclear risk | Comment: Reported as a double‐blind study; no other details reported |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: Reported as a double‐blind study; with "double dummy" blinding described for patients and physicians and other raters Quote: "To ensure that the treating physician and other raters remained unaware of drug administration, the nortriptyline dose was adjusted by a physician who was not involved in the study" and "the blind was maintained by selecting, on a random basis, patients receiving active paroxetine to have their nortriptyline placebo increased or decreased to mimic the dose adjustment for patients re3cigving active nortriptyline" (Roose 1998, pg. 288) |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: Reported as a double‐blind study; no other details reported |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: ITT with last observation carried forward |
| Selective reporting (reporting bias) | Unclear risk | Comment: Results and methods section consistent Comment: No protocol or design paper available |
| Other bias | High risk | Comment: authors of the study involved in design, analysis and reporting were employees of SmithKline Beecham Pharmaceuticals PA |